The platinum coordination complex cisplatin (cis-diamminedichloroplatinum (II)) is widely prescribed for the treatment of a variety of tumours (eg advanced testicular cancer, ovarian cancer, breast cancer and cancers of the bladder, head, neck, oesophagus and lung). Carboplatin (cis-diammine(1,1-cyclobutanedicarboxylato)platinum (II)) has similar antineoplastic activity and may also be used in bone marrow therapy or peripheral stem cell rescue. U.S. Pat. No. 4,177,263, the entire disclosure of which is incorporated herein by reference, describes methods of treating cancer with cisplatin and cisplatin analogues.
Cisplatin is classified as an alkylating agent. It is believed to kill cancer cells by covalently binding to DNA and interfering with its repair mechanism, eventually leading to cell death. After the cisplatin molecule enters the cell membrane, the first step is for a molecule of water to replace one of the chloride ions of the cisplatin molecule. The resulting complex can then bind to a nitrogen on a DNA nucleotide. The second chloride ion is then replaced by another water molecule and the platinum binds to a second nucleotide. Cisplatin has a preference for nitrogen 7 on two adjacent guanines on the same strand. It also binds to adenine and to a lesser extent across strands. The resulting distortion in shape of the DNA prevents effective repair.
Another covalent binder, oxaliplatin ([Pt(I)xalato (1R),(2R)-diaminocyclohexane] complex) is prescribed for treating the same type of cancers, more particularly cancers of the ovaries, as well as cancers of the colon, of the upper respiratory tracts and epidermoid cancers. Oxaliplatin belongs to the class of platinum(II)-trans-1,2-diaminocyclohexane complexes.